How did a deadly tropical fungus get to the temperate environs of the Pacific Northwest?

FLAGSTAFF, Ariz. -- Jan. 17, 2018 -- In what is being described as "The Teddy Roosevelt effect," a deadly fungus in the Pacific Northwest may have arrived from Brazil via the Panama Canal, according to a new study led by the Translational Genomics Research Institute (TGen).

Cryptococcus gattii -- which until a 1999 outbreak in British Columbia's Vancouver Island was considered primarily a tropical fungus primarily found in places like Brazil, New Guinea and Australia -- can cause deadly lung and brain infections in both people and animals.

Researchers used genomic analysis and advanced statistics to trace the likely evolution of the disease, correlating it in time to the 1914 opening of the Panama Canal and a surge of shipping trade between Brazil and the Pacific Northwest. The results were published today in the journal mSphere.

C. gattii infections first appeared in Washington in 2007, and in Oregon in 2010, with isolated incidences in Idaho and California. Symptoms include cough, shortness of breath, chest pain, fever, headache, neck pain, nausea, vomiting, sensitivity to light and confusion or changes in behavior. Treatment can include months of intravenous and oral anti-fungal drugs, and in some cases surgical removal from the lungs and central nervous system.

"Understanding the emergence and continual evolution of this pathogen into a new environment is critical to the understanding of the ongoing spread of cryptococcal disease, and may be important to studying the evolution of other emerging health threats," said Dr. David Engelthaler, Director of TGen's Pathogen and Microbiome Division, TGen North, in Flagstaff, and the study's senior author.

Researchers performed whole genome sequencing on 134 C. gattii samples. They then estimated fungal mutation rates and used evolutionary analysis to calculate the arrival of C. gattii in the Pacific Northwest within the past 60 to 100 years, which the authors posit, "makes a strong case for an anthropogenic (human-caused) introduction."

The source and timing of the emergence of C. gattii in the Pacific Northwest have been a challenge to public health researchers since cryptococcosis seemingly first appeared in British Columbia in 1999.

Nearly 3 million years ago, the Isthmus of Panama rose to create a land bridge between North and South America, and a barrier between the Atlantic and Pacific oceans.

The study results suggest that the completion of the Panama Canal in 1914 may have provided the perfect migratory path for the fungus. Trade between North and South America via the Panama Canal initially included hardwood lumber, minerals, coffee and rubber. However, researchers in this study propose that contaminated ballast water -- which has spread animals, algae and microbes across the globe -- is one hypothetical way C. gattii may have moved from Brazil to the Pacific Northwest. C. gattii fungus survives in seawater and has caused infections in marine mammals in the Pacific Northwest, and elsewhere.

"Whatever the cause of C. gattii to the PNW, it is clear that those populations are neither ancient nor very recent (less than 25 years) arrivals to the region," the authors state, and dispersal in the last 100 years "would strongly suggest" a human cause, rather than animal migrations, as proposed with the slower evolution and spread of Valley Fever and other disease-causing fungi. In a similar genomic-evolution study, TGen researchers last year determined that the Valley Fever fungus moved from North America to South America hundreds of thousands of years ago, after the formation of the land bridge, but well before humans were known to be in the Western Hemisphere.

"As North American populations of C. gattii continue to evolve and disperse, it will be useful to continually apply genomic dating to understand the nature of these events and the expanding impact of these fungi on human and veterinary health," Dr. Engelthaler said.

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Contributing to this study were: Washington State Health Department, Oregon Health Authority, Canada's Institut National de Sante Publique du Quebec, Canadian Wildlife Heath Cooperative, Brazil's National Institute of Infectious Diseases, Australia's Institute for Emerging Infections and Biosecurity, the U.S. Centers for Disease Control and Prevention, University of California-Davis, and Northern Arizona University.

The study -- Dating the Cryptococcus gattii Dispersal to the North American
Pacific Northwest -- was supported by grants from: the U.S. Centers for Disease Control and Prevention, the National Institutes of Health, and Australia's National Health and Medical Research Council.

About TGen

Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research with life changing results. TGen is focused on helping patients with neurological disorders, cancer, diabetes, and infectious diseases, through cutting edge translational research (the process of rapidly moving research towards patient benefit). TGen physicians and scientists work to unravel the genetic components of both common and rare complex diseases in adults and children. Working with collaborators in the scientific and medical communities literally worldwide, TGen makes a substantial contribution to help our patients through efficiency and effectiveness of the translational process. TGen is affiliated with City of Hope, a world-renowned independent research and cancer and diabetes treatment center: http://www.cityofhope.org. This precision medicine affiliation enables both institutes to complement each other in research and patient care, with City of Hope providing a significant clinical setting to advance scientific discoveries made by TGen. For more information, visit: http://www.tgen.org. Follow TGen on Facebook, LinkedIn and Twitter @TGen.

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